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Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis (ASTRUM)

Primary Purpose

Ankylosing Spondylitis

Status

Completed

Phase

Phase 4

Locations

Germany

Study Type

Interventional

Intervention

Secukinumab (AIN457) 150 mg s.c.

Placebo - Secukinumab (AIN457) 150 mg s.c.

About this trial

This is an interventional treatment trial for Ankylosing Spondylitis focused on measuring Ankylosing Spondylitis, NSAID, ASAS, ASAS-NSAID score, Secukinumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Diagnosis of active AS with prior documented radiologic evidence fulfilling the Modified New York criteria for AS
Active AS assessed by total BASDAI ≥ 4 (0-10) at baseline
Spinal pain as measured by BASDAI Question 2 ≥ 4 cm on a 0-10 cm numeric rating scale at baseline
Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline
Patients should have been on at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks prior to randomization, with an inadequate response or failure to respond, or less if therapy had to be reduced due to intolerance, toxicity or contraindications
Patients must report regular intake of NSAIDs of at least 50% of the highest recommended dose at Screening.
Patients with prior TNFα inhibitor therapy must report regular intake of NSAIDs of at least 50% of the highest recommended dose at baseline after the appropriate washout
Patients are required to be on a stable dose of NSAIDs for at least 2 weeks before randomization
Patients who have previously been on a TNFα inhibitor will be allowed entry into study after an appropriate wash-out period prior to randomization
Patients who have been on a TNFα inhibitor (not more than two) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to randomization or have been intolerant to at least one administration of an anti-TNFα agent.
Patients taking MTX or sulfasalazine are allowed to continue their medication and must have taken it for at least 3 months and be on a stable dose for at least 4 weeks prior to randomization

Key Exclusion Criteria:

Chest X-ray or MRI with evidence of ongoing infectious or malignant process.
Previous exposure to Secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor
Patients previously treated with any biological immunomodulating agents, except those targeting TNFα
Patients who have taken more than two anti-TNFα agents
Pregnant or nursing (lactating) women.
History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.
Patients who are intolerant to NSAIDs

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Secukinumab - delayed NSAID tapering

Secukinumab - early NSAID tapering

Placebo

Arm Description

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.

Outcomes

Primary Outcome Measures

Proportion of Patients Who Achieved ASAS20 Response in the Pooled Secukinumab Group Compared With the Placebo Group at Week 12

ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and inflammation represented by mean duration and severity of morning stiffness. Non-responder imputation was applied for missing data.

Secondary Outcome Measures

Proportion of Patients Who Achieved ASAS20 Response in Each Secukinumab Group (Delayed NSAID Tapering and Early NSAID Tapering) Compared With the Placebo Group

Mean Change From Baseline in ASAS-NSAID Score at Week 12

ASAS-NSAID score is used to present the NSAID (nonsteroidal anti-inflammatory drug) intake by considering the type of NSAID, the total dose and the number of days taking NSAID during a period of interest (PI). For the NSAID equivalence scoring system, "no NSAID intake" was set to a score value of 0, and the reference dose of 150 mg/day diclofenac was set to a score value of 100. The Daily diclofenac-equivalent dose score was derived by converting each daily dose of NSAID to a percentage dose equivalent of 150 mg diclofenac. ASAS-NSAID score = (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days). A negative change from baseline indicates less NSAID consumption.

Mean Change From Baseline in ASAS-NSAID Score in Each Secukinumab Group After 12 Weeks of Exposure (at Week 12 in the Secukinumab-delayed NSAID Tapering Group and at Week 16 in the Secukinumab-early NSAID Tapering Group)

Mean Change From Baseline in the BASDAI Total Score

The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to ankylosing spondylitis: 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (captured as a continuous visual analog scale). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe symptoms. A negative change from baseline in the total 0-10 BASDAI score indicates improvement.

Mean Change From Baseline in Health-related Quality of Life as Measured by the Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score

The Short Form-36 Health Survey (SF-36) measures the impact of disease on overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36 (SF-36 PCS) that is evaluated in this study. Scores on each item 1-4 were summed and averaged (range = 0-100 with higher scores indicating better levels of function and/or better health). A positive change from Baseline indicates improvement.

Full Information

NCT ID

NCT02763046

First Posted

May 3, 2016

Last Updated

October 7, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02763046

Brief Title

Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis

Acronym

ASTRUM

Official Title

A Randomized, Double-blind, Placebo-controlled Multicenter Study of Secukinumab (AIN457) to Examine the Clinical Efficacy and the NSAID-sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis (ASTRUM)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

May 31, 2016 (Actual)

Primary Completion Date

September 24, 2019 (Actual)

Study Completion Date

September 24, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This study assessed the clinical Assessment of SpondyloArthritis international Society (ASAS) 20 response to secukinumab and evaluated to which extent concomitant nonsteroidal anti-inflammatory drug (NSAID) treatment can be reduced in patients treated with secukinumab or placebo following an initial run-in phase of stable NSAID therapy.

Detailed Description

This was a phase IV, 20-week, randomized, double-blind, 3-arm, placebo-controlled, parallel-group, multicenter study to examine the clinical response of secukinumab treatment in patients with ankylosing spondylitis as measured by the Assessment of SpondyloArthritis international Society (ASAS) 20 response and the nonsteroidal anti-inflammatory drug (NSAID)-sparing effect. This study evaluated to which extent nonsteroidal anti-inflammatory drug (NSAID) treatment can be reduced between Week 4 and Week 12 in patients randomized to secukinumab 150 mg or placebo following an initial run-in phase of 4 weeks on stable NSAID therapy. Two NSAID tapering approaches were evaluated in this study: an early tapering approach in which NSAID were tapered at the start of secukinumab treatment, a delayed tapering approach in which NSAID were tapered following 4 weeks of secukinumab treatment. Patients were randomized 1:1:1 to one of the following treatment groups: Secukinumab - delayed NSAID tapering: Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering). Secukinumab - early NSAID tapering: Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering). Placebo: Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4. The primary objective of the study was to demonstrate that the efficacy of secukinumab 150 mg subcutaneous (s.c.) injection (with NSAID tapering) is superior to placebo based on the proportion of patients achieving an ASAS20 response at Week 12. To show superiority, both secukinumab treatment arms were pooled and compared against placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ankylosing Spondylitis

Keywords

Ankylosing Spondylitis, NSAID, ASAS, ASAS-NSAID score, Secukinumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

211 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Secukinumab - delayed NSAID tapering

Arm Type

Experimental

Arm Description

Arm Title

Secukinumab - early NSAID tapering

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Secukinumab (AIN457) 150 mg s.c.

Intervention Description

Induction: 5 x 150 mg secukinumab s.c. weekly Maintenance: 4 x 150 mg secukinumab s.c. every 4 weeks Delayed NSAID tapering (tapering following 4 weeks of secukinumab treatment).

Intervention Type

Drug

Intervention Name(s)

Secukinumab (AIN457) 150 mg s.c.

Intervention Description

Induction: 5 x 150 mg secukinumab s.c. weekly Maintenance: 3 x 150 mg secukinumab s.c. every 4 weeks Early NSAID tapering (tapering at the start of secukinumab treatment).

Intervention Type

Drug

Intervention Name(s)

Placebo - Secukinumab (AIN457) 150 mg s.c.

Intervention Description

Placebo for 15 weeks. From Week 16 on, 5 x 150 mg secukinumab s.c. weekly.

Primary Outcome Measure Information:

Title

Proportion of Patients Who Achieved ASAS20 Response in the Pooled Secukinumab Group Compared With the Placebo Group at Week 12

Description

Time Frame

Baseline, Week 12

Secondary Outcome Measure Information:

Title

Proportion of Patients Who Achieved ASAS20 Response in Each Secukinumab Group (Delayed NSAID Tapering and Early NSAID Tapering) Compared With the Placebo Group

Description

Time Frame

Baseline, Week 12, Week 16

Title

Mean Change From Baseline in ASAS-NSAID Score at Week 12

Description

Time Frame

Baseline, Week 12

Title

Description

Time Frame

Baseline, Week 12 (delayed NSAID tapering), Week 16 (early NSAID tapering)

Title

Mean Change From Baseline in the BASDAI Total Score

Description

Time Frame

Baseline, Week 12, Week 16

Title

Mean Change From Baseline in Health-related Quality of Life as Measured by the Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score

Description

Time Frame

Baseline, Week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Diagnosis of active AS with prior documented radiologic evidence fulfilling the Modified New York criteria for AS Active AS assessed by total BASDAI ≥ 4 (0-10) at baseline Spinal pain as measured by BASDAI Question 2 ≥ 4 cm on a 0-10 cm numeric rating scale at baseline Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline Patients should have been on at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks prior to randomization, with an inadequate response or failure to respond, or less if therapy had to be reduced due to intolerance, toxicity or contraindications Patients must report regular intake of NSAIDs of at least 50% of the highest recommended dose at Screening. Patients with prior TNFα inhibitor therapy must report regular intake of NSAIDs of at least 50% of the highest recommended dose at baseline after the appropriate washout Patients are required to be on a stable dose of NSAIDs for at least 2 weeks before randomization Patients who have previously been on a TNFα inhibitor will be allowed entry into study after an appropriate wash-out period prior to randomization Patients who have been on a TNFα inhibitor (not more than two) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to randomization or have been intolerant to at least one administration of an anti-TNFα agent. Patients taking MTX or sulfasalazine are allowed to continue their medication and must have taken it for at least 3 months and be on a stable dose for at least 4 weeks prior to randomization Key Exclusion Criteria: Chest X-ray or MRI with evidence of ongoing infectious or malignant process. Previous exposure to Secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor Patients previously treated with any biological immunomodulating agents, except those targeting TNFα Patients who have taken more than two anti-TNFα agents Pregnant or nursing (lactating) women. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection. Patients who are intolerant to NSAIDs

Facility Information:

Facility Name

Novartis Investigative Site

City

Bad Doberan

ZIP/Postal Code

18209

Country

Germany

Facility Name

Novartis Investigative Site

City

Bayreuth

ZIP/Postal Code

95444

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

12161

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

12163

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

13055

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

13125

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

14059

Country

Germany

Facility Name

Novartis Investigative Site

City

Chemnitz

ZIP/Postal Code

09130

Country

Germany

Facility Name

Novartis Investigative Site

City

Cottbus

ZIP/Postal Code

03042

Country

Germany

Facility Name

Novartis Investigative Site

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Novartis Investigative Site

City

Elmshorn

ZIP/Postal Code

25335

Country

Germany

Facility Name

Novartis Investigative Site

City

Erlangen

ZIP/Postal Code

91056

Country

Germany

Facility Name

Novartis Investigative Site

City

Frankfurt am Main

ZIP/Postal Code

60528

Country

Germany

Facility Name

Novartis Investigative Site

City

Freiberg

ZIP/Postal Code

09599

Country

Germany

Facility Name

Novartis Investigative Site

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Novartis Investigative Site

City

Gottingen

ZIP/Postal Code

37075

Country

Germany

Facility Name

Novartis Investigative Site

City

Hamburg

ZIP/Postal Code

22081

Country

Germany

Facility Name

Novartis Investigative Site

City

Hamburg

ZIP/Postal Code

22143

Country

Germany

Facility Name

Novartis Investigative Site

City

Hamburg

ZIP/Postal Code

22415

Country

Germany

Facility Name

Novartis Investigative Site

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Novartis Investigative Site

City

Herne

ZIP/Postal Code

44649

Country

Germany

Facility Name

Novartis Investigative Site

City

Koeln

ZIP/Postal Code

51149

Country

Germany

Facility Name

Novartis Investigative Site

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Novartis Investigative Site

City

Leipzig

ZIP/Postal Code

04109

Country

Germany

Facility Name

Novartis Investigative Site

City

Lubeck

ZIP/Postal Code

23538

Country

Germany

Facility Name

Novartis Investigative Site

City

Magdeburg

ZIP/Postal Code

39104

Country

Germany

Facility Name

Novartis Investigative Site

City

Magdeburg

ZIP/Postal Code

39110

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

ZIP/Postal Code

81541

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

ZIP/Postal Code

81675

Country

Germany

Facility Name

Novartis Investigative Site

City

München

ZIP/Postal Code

80331

Country

Germany

Facility Name

Novartis Investigative Site

City

Nienburg

ZIP/Postal Code

31582

Country

Germany

Facility Name

Novartis Investigative Site

City

Nuernberg

ZIP/Postal Code

90443

Country

Germany

Facility Name

Novartis Investigative Site

City

Püttlingen

ZIP/Postal Code

66346

Country

Germany

Facility Name

Novartis Investigative Site

City

Rendsburg

ZIP/Postal Code

24768

Country

Germany

Facility Name

Novartis Investigative Site

City

Saarbruecken

ZIP/Postal Code

66111

Country

Germany

Facility Name

Novartis Investigative Site

City

Schwerin

ZIP/Postal Code

19055

Country

Germany

Facility Name

Novartis Investigative Site

City

Sendenhorst

ZIP/Postal Code

48324

Country

Germany

Facility Name

Novartis Investigative Site

City

Trier

ZIP/Postal Code

54292

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Links:

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=716

Description

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis

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Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis (ASTRUM)

Ankylosing Spondylitis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial